A study of the inheritance of the central and peripheral optical properties in the human eye

espanolEn las ultimas decadas se ha observado un aumento en la incidencia global de la miopia. La refraccion periferica relativa ha sido ampliamente utilizada en diversos estudios que buscan comprender la causa de la progresion de la miopia y su posible prevencion. En esta tesis se investiga la varianza de los fenotipos de calidad optica central y periferica, como el error refractivo, las aberraciones de alto orden y parametros biometricos del ojo, en una poblacion de gemelos jovenes reclutada por el Registro de Gemelos de Murcia. Se incluyeron 200 hermanos gemelos jovenes, incluyendo 54 parejas de gemelos monocigoticos (MZ) y 46 dicigoticos (DZ). Se midieron las aberraciones oculares a partir de series de imagenes de un sensor de frente de onda Hartmann-Shack (HS) y el error refractivo objetivo (M). Tambien se midieron la refraccion (EE) y la agudeza visual. Se uso un sensor de frente de onda periferico operando en vision abierta (VPR, Voptica SL, Murcia, Espana) para medir las aberraciones en la periferia (±40 grados). Los parametros biometricos oculares se midieron utilizando un biometro Haag-Streit Lenstar LS900 (Haag-Streit AG, Koniz, Suiza). Para comparar el error refractivo se analizaron los resultados para estas tres zonas retinianas: linea de mirada (MLOS), periferia media (Mmid-periphery), y periferia relativa (Mrelative-periphery). El perfil de refraccion central se analizo utilizando el error cuadratico medio (RMSEPRO) y la asimetria nasal-temporal (RMSEASY). Los sujetos del estudio mostraron una alta prevalencia de miopia (77 %). Los resultados de SE mostraron una correlacion similar entre las parejas MZ (75 %) y DZ (68 %), lo que sugiere un efecto combinado de la genetica y del entorno sobre la variacion de este rasgo. El modelo de ecuaciones estructurales (SEM) revelo que mas de la mitad de la proporcion de la variacion del cambio de error de refraccion, tanto en la LOS como en la periferia media, se explicaba por la variacion en el entorno compartido (C), con solo un cuarto por la variacion en la genetica aditiva. Para la refraccion periferica, el modelo tenia una influencia genetica aditiva (A; 0,47) con una disminucion de la influencia ambiental compartida (C; 0,24). Sin embargo, los cambios en la refraccion periferica o la zona retiniana de la periferia relativa se ajustaron mejor con un modelo principalmente genetico (AE): el modelo mostro que la proporcion de la varianza de la refraccion periferica relativa explicada por la genetica aditiva fue de 0,82. El analisis de la imagen periferica mostro una correlacion mayor entre los gemelos MZ (RMSEPRO, 68 %; RMSEASY, 65 %) que entre los gemelos DZ RMSEPRO, 23 %; RMSEASY, 16 %. El analisis SEM correspondiente mostro que el modelo que mejor se ajustaba era un AE, que describia la mitad de su varianza por genetica aditiva (A) y la otra mitad por exposiciones ambientales unicas, mas errores (E). El tamano del ojo en la linea de vision (ALLOS) mostro una mayor correlacion para los gemelos MZ (90 %) que para los gemelos DZ (61 %), siendo ambos similares a los encontrados fuera del eje (AL14 y AL20), con valores de correlacion que van desde 89 a 93 % en gemelos MZ y de 59 a 60 % en gemelos DZ, lo que indica una influencia mixta genes-medio ambiente para explicar su varianza. Nuestra poblacion de estudio presenta una mayor prevalencia de miopia. Sin embargo, la tendencia general de la periferia no cambio con el desarrollo de la miopia, posiblemente debido al menor impacto del crecimiento ocular en la periferia. La varianza del segmento anterior del ojo muestra un fuerte impacto genetico. Mientras que los componentes oculares posteriores pierden su heredabilidad. EnglishDuring the last three decades, a sudden outbreak of global myopia prevalence has been observed worldwide. Relative peripheral refraction has been widely discussed in recent studies in order to understand the root cause of myopia progression and its possible prevention. Recent studies found that the myopic individuals had relative hyperopic defocus in the peripheral retina, whereas emmetropic and hyperopic individuals had relative peripheral myopic defocus. This thesis was designed to investigate the variance of central and peripheral refractive error, higher-order aberrations, and biometric eye measurements in a young twin population registered with the Murcia twin registry, Spain. 100 twin pairs were included in this study with 54 monozygotic (MZ) and 46 dizygotic (DZ) twins. Manifest refraction (SE) and on-axis aberrations (LOA & HOA) were measured using a visual adaptive optics simulator (VAO, Voptica SL, Murcia, Spain). An open-view fast scanning Hartmann-Shack (HS) peripheral wavefront sensor (VPR, Voptica SL, Murcia, Spain) was used to measure the peripheral wavefront aberrations (± 35 degrees). Ocular biometric parameters were measured using Haag-Streit Lenstar LS900 (Haag-Streit AG, Koniz, Switzerland). The refraction zones were divided into three retinal areas: central measurement at line of sight (MLOS); Mid-periphery zone (Mmid-periphery) and relative periphery zone (Mrelative-periphery). The central peripheral refraction profile was further analyzed using root mean square error (RMSEPRO) and nasal-temporal asymmetry (RMSEASY). Our study subjects showed a high prevalence of myopia (77%) and the average SE was -2.0±2.0 [+3.8 to -7.0] in MZ and -2.2±2.1 D [0.0 to -9.8] in DZ twins. For manifest refraction (SE), the result showed similar intraclass correlation coefficient (ICC) values among MZ (75 %) and DZ (68 %) twin groups, suggesting a combined effect of gene and environment. The structural equation model (SEM) revealed more than half of the refraction variation at MLOS and Mmid-periphery were explained mainly by shared environmental (C) effect with only one quarter by additive genetics (A). The Mrelative-periphery showed relatively greater additive genetic control (A; 0.47) with decreased shared environmental influence (C; 0.24). The model fitting showed the relative peripheral refraction variance being explained in 0.82 by additive genetics. The peripheral image shell analysis showed relatively higher ICC among MZ twins (RMSEPRO = 68 %, RMSEASY = 65 %) than DZ (RMSEPRO = 23 %, RMSEASY = 0.16 %). The SEM showed best fitting being an AE model, describing half of the variation by additive genetics (A) and the remaining half by unique environmental influence (E). The ALLOS showed higher correlation (90 %) in MZ twins than DZ (61 %), being similar to those found off-axis (AL14 & AL20), with correlations ranging from 89 to 93 % in MZ and from 59 to 60 % in DZ twins, indicating a gene-environmental mixed influence on the variance for all the eye size traits. The biometric variance at anterior segment of the eye has shown strong genetic impact. Whereas, axial length losses its heritability by the influence of visual environmental exposures in association with axial elongation of the eye. We can conclude as the variance of manifest on-axis refraction within the study population of young twins showed a significant influence of shared environment with minimal additive genetic control. Over time, due to shared environmental influences, our study population developed a higher prevalence of myopia. However, the general trend of in the periphery didn't change with myopia development, possibly because of the lesser impact of eye growth in the periphery. The variance at the anterior segment distances of the eye showed a strong genetic impact. Whereas, the posterior ocular components losses its heritability by the influence of visual environmental exposures in association with axial elongation of the eye.